Delivery system and method for interstitial radiation therapy using strands constructed with extruded strand housings

ABSTRACT

A delivery system and method for interstitial radiation therapy comprising substantially axially stiff and longitudinally flexible elongated members made of material which is bioabsorbable in living tissue and a plurality of radioactive seeds dispersed in a predetermined array within the elongate member. The radioactive seeds can be dispersed within assembled half-shells made of the same material. The housing for the radiation seeds can also be manufactured from extruded material. A system for manufacturing the interstitial radiation therapy seed strands that automatically makes the seed strands at the patient&#39;s bedside. The delivery system and method further customize the member based on a prescription.

CLAIM OF PRIORITY

This application claims priority under 35 U.S.C. 119(e) to U.S.Provisional Application No. 60/336,329, filed Nov. 2, 2001 and U.S.Provisional Application No. 60/360,272, filed Feb. 26, 2002, each ofwhich is incorporated herein by reference.

CROSS-REFERENCE TO RELATED APPLICATIONS

U.S. Provisional Patent Application No. 60/360,241 entitled “DeliverySystem and Method for Interstitial Radiation Therapy Using Seed StrandsConstructed With Preformed Strand Housing,” by Terwilliger et al., filedFeb. 26, 2002. (WORLD-01000US2)

U.S. Provisional Patent Application No. 60/360,237 entitled “System forManufacturing Interstitial Radiation Therapy Seed Strands,” byTerwilliger et al., filed Feb. 26, 2002. (WORLD-01000US3)

U.S. Provisional Patent Application No. 60/360,299 entitled “DeliverySystem and Method for Interstitial Radiation Therapy Using Seed ElementsWith Ends Having One of Projections and Indentations,” by Terwilliger etal., filed Feb. 26, 2002. (WORLD-01003US0)

U.S. Provisional Patent Application No. 60/360,260 entitled “DeliverySystem and Method for Interstitial Radiation Therapy,” by Terwilliger etat., filed Feb. 26, 2002. (WORLD-01004US0)

FIELD OF INVENTION

The present invention relates to systems and methods for delivering aplurality of radioactive sources to a treatment site.

BACKGROUND

In interstitial radiation therapy one method for treating tumors is topermanently place small, radioactive seeds into the tumor site. Thismethod is currently accomplished by one of the following two procedures:(a) loose seeds are implanted in the target tissue, and/or (b) seeds arecontained within a woven or braided absorbable carrier such as braidedsuture material and implanted in the target tissue. The loose seeds,however, are dependent on the tissue itself to hold each individual seedin place during treatment, and the woven or braided sutures do notassist in the placement of the seeds relative to the target tissue.

There have been many developments in brachytherapy (i.e. therapyrelating to treating malignant tumors with such radioactive seeds). Inone technique, hollow metal needles are inserted into the tumor and theseeds are thereafter inserted into the needles, while the needles arebeing retracted to deposit the seeds in the tumor at the desiredlocations. Such devices are shown in U.S. Pat. No. 4,402,308 which isincorporated herein by reference. The most commonly used instruments arethe Henschke and Mick devices. The use of such devices has distinctdisadvantages. The overall length of such devices is over 20 cm and suchdevices have significant weight making them difficult to manipulate.

Another disadvantage of the above technique is that the seeds aredeposited in a track made by the needle. When the needle is withdrawn,there is a tendency for the seeds to migrate in that track resulting ina poor distribution of the seeds. Because the energy levels are low,distribution between centers of adjacent seeds should be on the order ofabout 1 cm for certain treatments. Poor distribution of seeds can resultin undesirable concentrations of seeds resulting in either anover-dosage or an under-dosage of radiation. Additionally, over time,the seeds tend to migrate along the needle track, away from the tumor,and accordingly patients commonly must repeat the procedure within acouple months to have seeds re-implanted near the tumor.

Further complicating the procedure is the fact that the seeds are small,because they need to fit in small bore needles to prevent excessivetissue damage. Due to their small size and high seed surface dose, theseeds are difficult to handle and to label, and can easily be lost. Inaddition, the technique of implantation of individual seeds is timeconsuming.

One preferred method of introducing seeds into the tumor site is using apre-manufactured elongated assembly or implant that contains seedsspaced between spacers at 1 cm increments. This assembly is capable ofbeing loaded into an introducer needle just prior to the procedure. Whatis desired in using an elongated assembly of seeds and spacers is theability to insert such an assembly into a tumor site to providecontrolled and precise placement of the radioactive seeds.

While assemblies with bio-absorbable materials and spaced radioactiveseeds are known for use as interstitial implants, such assemblies arenot entirely satisfactory. In one instance, the elongated implant ismade using a bio-absorbable material consisting of an EthiconVicryl.RTM. This material is commonly known as PGA. Radioactive seedsand teflon spacers are inserted into the material. Needles loaded withthe seeds in the carrier bio-absorbable material are sterilized orautoclaved causing contraction of the carrier material and resulting ina rigid column of seeds and spacers. This technique was reported in“Ultrasonically Guided Transperineal Seed Implantation of the Prostate:Modification of the Technique and Qualitative Assessment of Implants” byVan't Riet, et al., International Journal of Radiation Oncology, Biologyand Physics, Vol. 24, No. 3, pp. 555–558, 1992 which is incorporatedherein by reference. Such rigid implants have many drawbacks, includingnot having the ability to flex with the tissue over the time that thebio-absorbable material dissolves.

As the tissue or glands being treated shrink back to pre-operative size,and thus as the tissue recedes, a rigid elongated implant does not movewith the tissue, but remains stationary relative to the patient. Thefinal location relative to the tumor is thus not maintained and thedosage of the radioactive seeds does not meet the preoperative therapyplan.

Another system for providing an elongated implant having radioactiveseeds disposed therein is disclosed in U.S. Pat. No. 4,697,575 which isincorporated herein by reference. In this reference, a plurality ofencapsulated radioactive seeds are positioned in a predetermined array.The seeds are encapsulated in individual capsules, with each capsulehaving a projection on one capsule end and a complementary recess on theremaining capsule end. A projection in one capsule is engageable with arecess in an adjacent capsule such that the desired number of seeds canbe plugged together to form a column of rigid, bio-absorbable andelongated material. This implant is not entirely satisfactory in as muchas it is time consuming and inefficient to carry out the manipulativesteps of assembling such a strand of elongated material. Further theimplant is quite rigid as it is inserted into a patient without the useof an introduction needle, as the implant itself acts as a rigid needlethat is undesirably left in place.

In another embodiment disclosed in the above patent, a rigid needleimplant containing radioactive segments, with break points, is insertedinto the tumor. The needle implant is made of a bio-absorbable polymerthat is rigid enough to be driven into the tumor without deflection andwithout the use of a separate hollow needle. When the proper depth isreached with the rigid polymer needle, the remaining, uninserted portionof the needle is broken off. This embodiment has the disadvantage of theabove embodiment. As the implant is too rigid, the implant does notfollow the tumor as it shrinks back to its normal size.

In U.S. Pat. No. 6,163,947, Coniglione, issued Dec. 26, 2000, andincorporated herein by reference, a string of hollow seeds described inU.S. Pat. No. 5,713,828, issued Feb. 3, 1998, also incorporated hereinby reference, are strung onto a thin strand of suture material to forman array of seeds. This string of seeds is delivered into the tumor siteplaced within a hollow needle. Since the hollow lumen of the seeds aresubstantially smaller in diameter in relation to the outside diameter ofthe seed body, the string of suture material must be substantiallysmaller in diameter than the seeds themselves. The resulting diameter ofthe suture makes the suture axially weak and the suture can fold upbetween the seeds within the needle lumen as pressure is applied on theproximal end of the strand within the needle. Thus the difference indiameter between the seed and the thin suture material makes theassembly susceptible to collapse from axial force applied on theproximal end, resulting in jamming of the assembly within the needlelumen and/or the assembly not maintaining the proper desired spacingbetween radioactive seeds as the assembly is expelled into the treatmentsite.

One relevant reference discloses modification of the needle structure toinclude a reloadable cartridge. In such reference the needle is insertedand as a cartridge of seeds is emptied, the plunger of the device iswithdrawn and a new cartridge containing radioactive seeds is loadedinto the syringe (Moore, U.S. Pat. No. 4,086,914, issued May 2, 1978).Another reference offers a device for implanting individual seeds in aplanar dispensing device with multiple needles to ensure accurateplacement of the seeds relative to one another and the treatment site(Kirsch, U.S. Pat. No. 4,167,179 issued September 1979). Anotherreference disclosed a shielding devices for bead strands which preventsradiation exposure for health care personnel performing treatment withthe radioactive seeds (Windarski, U.S. Pat. No. 4,509,506 issued April1985). All of the above references are incorporated herein by reference.

In another technique for treating tumors disclosed in U.S. Pat. No.5,460,592 and incorporated herein by reference, seeds are held in awoven or braided bio-absorbable carrier such as a braided suture. Thecarrier with the seeds laced therein is then secured in place to form asuitable implant. This braided assembly exhibits many drawbacks, as andwhen the braided assembly is placed into the tumor. The needle thatcarries the braided assembly must be blocked at the distal end toprevent body fluids from entering the lumen. If body fluid reaches thebraided assembly while the assembly is still in the lumen of the needle,the braided assembly can swell and jam in the lumen. Because theassembly is made of a braided tubular material, it is difficult to pushthe assembly out of the needle. As the needle is withdrawn from thetumor, pressure on the proximal end of the braided assembly causes thebraid to expand and jam inside the lumen of the needle. Finally, if thebraided strand is successfully expelled from the needle, the relativespacing of the seeds may not be maintained, if the braided material hascollapsed.

Another apparatus for automated production of brachytherapy devices isthe Mentor Isoloader™. The Isoloader™ consists of an interface tocommercial treatment planning systems, a shielded seed cartridge, ashielded needle cartridge, a shielded needle holder and a radiationdetector for seed assay. The Isoloader™ picks the radioactive seeds,tests each one for radiation and then automatically loads the seed intoa needle. The apparatus provides for automated loading and verificationof radioactive seeds into needles. With the Isoloader™ system, theclinician plans the treatment for a specific patient using standardsoftware, and orders brachytherapy seeds of a suitable quantity andactivity level for that patient. The seeds are shipped to the clinicianin a pre-sterilized cartridge with a memory chip containing theindividual data and seed specifications. The cartridge is inserted intothe Isoloader™, and the seeds are automatically loaded into the surgicalneedles according to the treatment plan. The Isoloader™ produces a rigidneedle system that does not move with the tissue, as the tumor shrinksduring treatment.

Other references that address such implants and materials include thefollowing, all of which are incorporated herein by reference.

U.S. Patent Documents:

-   U.S. Pat. No. 1,578,945 issued January 1923 to Withers-   U.S. Pat. No. 2,067,589 issued January 1937 to Antrim-   U.S. Pat. No. 3,351,049 issued November 1967 to Lawrence-   Medi-Physics brochure entitled “I-125 Seeds.RTM. In Carrier”, Model    No. 6720.-   Medi-Physics brochure entitled “I-125 Seed.RTM. Source Model 6711”.-   Martinez et al., Int. J. Radiation Oncology Biol. Phys., vol. 5, No.    3, March 1979, pp. 411–413.

SUMMARY OF SOME OF THE ASPECTS OF THE INVENTION

Accordingly, the present invention cures and addresses the disadvantagesexhibited in the prior art devices and implants. What is desired is toprovide a bio-absorbable carrier material having seeds disposed withinthe material, with the seeds being accurately spaced a predetermineddistance from one another, with the seeds repeatably maintaining thatspacing, even after being introduced into the body.

It is further desired that an elongated member with seeds besufficiently rigid axially to allow expulsion of the member whilemaintaining the spacing between seeds, and that the member be flexibleand pliable enough to move with the tissue as the tissue shrinks back topre-operative size.

Accordingly, some of the objectives of the present invention includeproviding an elongated member with seeds dispersed throughout, whichobviates the aforementioned disadvantages and allows placement of theseeds in accurate positions to provide the desired interstitialradiation dose to the location derived from a preoperative dosimeterplan.

A further object of the present invention is to provide a deliverysystem for interstitial radiation therapy, which is faster and easier touse than prior art systems.

Another object of the present invention is a delivery system that causesa minimum of trauma to tissue.

Yet another object of the present invention is a delivery system thatallows for control of the radiation dosage given the tissue. Stillfurther objects of the present invention is a delivery system that canbe used and placed with precision, and that maintains the position ofthe implant after the implantation, until the bio-compatible materialdissolves and the seeds have become inert. In another aspect thebio-compatible material is selected to absorb about when the half-lifeof the radioactive seeds is reached.

A further aspect is to have the implant be echogenic.

In accordance with an embodiment of the invention, the delivery systemcomprises a substantially axially stiff and longitudinally flexibleelongated member that is bio-absorbable in living tissue. The member hasa length that greatly exceeds its width or diameter. The elongatedmember has a plurality of radioactive seeds dispersed therein in apredetermined array.

In another embodiment, the substantially axially stiff and radiallyflexible elongated member comprises a single continuous monofilamentelement of bio-compatible material that has a plurality of seed sourcesmolded therein. The bio-compatible material can be preferably abio-absorbable polymer or copolymer material that encapsulates theplurality of radioactive seeds.

A further embodiment of the invention is characterized as asubstantially constant diameter elongated member of a bio-absorbablepolymer with seeds positioned therein at predetermined spacing along itslength, whose diameter is a close fit to the needle lumen, thuspreventing collapse as axial force is applied on the proximal end of theelongated member. The space between the seed sources is maintainedthroughout the insertion and expulsion of the elongated member. Thediameter of the polymer between the seeds may be slightly reduced inrelation to the overall diameter of the elongated member, but is ofsufficient diameter so as to not allow collapse of the member within theneedle lumen.

The present embodiment of the invention further allows for variation inany spacing between seeds, as the semi-rigid, deflecting elongate membercan be produced under a doctor's prescription for each patient, withoptimal seed distribution for a particular patient's treatment program.

Thus an object of the invention is to provide an implant that can becustom made as specified by a prescription for an individual patient.

It is also desired that the present invention provide for elongatemembers shaped like half-shells. Radioactive or other seed elementsand/or spacers can then be placed within one half-shell. The emptyhalf-shell is then mated to the half-shell containing the seed elementsor spacers, with the two half-shells now forming a tube structure thatcontains the seed elements and spacers. Then the half-shells are heated,causing them to fuse into a single therapeutic element and fixing theseeds and spacers within the therapeutic element. The resultingtherapeutic element is axially rigid and radially flexible. Twohalf-shells can also be assembled as described above containing the seedelements and spacers and liquid material flowed into the assembledhalf-shell. The liquid material then solidifies, fusing the half-shellsand fixing the seed elements and spacers inside. The solidified materialis axially rigid and radially flexible and may be a bio-absorbablepolymer.

In another embodiment, liquid polymer is flowed into a half-shell intowhich has previously been placed seeds. The polymer can solidify at theother half-shell is placed in contrast with the first half-shell. Theassembly can be heated so the assembly fuses together.

Another object of the present invention is to provide a bedsideapparatus that produces interstitial radiation therapy seed strands madeof a material having seeds disposed within the material with the seedsbeing accurately spaced a predetermined distance from one another.

The present invention cures and addresses the disadvantages exhibited inthe prior art devices, implants and manufacturing devices and methods.It is also desired to provide a device and method that extrudes abio-absorbable carrier material into an elongate hollow member and loadsseeds within the bore of the extruded material, during or afterextrusion, with the seeds being accurately spaces a predetermineddistance from one another, and the seeds repeatably maintaining thatspacing, even after being introduced into the body.

Further aspects, objects, advantage and embodiment of the invention canbe understood from the specification, the figures and the claims.

DESCRIPTION OF THE DRAWINGS

The Embodiments of FIGS. 1A through 1C Represent a Delivery System andMethod for Interstitial Radiation Therapy

FIG. 1A is an enlarged side view of an embodiment of the therapeuticimplant of the invention.

FIG. 1B is an enlarged view of a cross-section of an embodiment of thetherapeutic implant of the invention of FIG. 1.

FIG. 1C is an enlarged side view of the brachytherapy device includingthe implant of FIG. 1A.

The Embodiments of FIGS. 2A through 2E Represent a InterstitialRadiation Therapy Seed Strands Constructed with Half-Shell StrandHousings

FIG. 2A is an enlarged side view of an embodiment of the half-shell andradioactive seed elements and spacers of the invention.

FIG. 2B is an enlarged side view of an embodiment of the assembledtherapeutic implant of the invention similar to FIG. 2A.

FIG. 2C is an enlarged side view of another embodiment of thehalf-shells and radioactive seed elements of the invention.

FIG. 2D is an enlarged side view of the brachytherapy device with twohalf-shells with indentations for seed elements.

FIG. 2E is an enlarged side view of two mated half-shells with seedelements placed in indentations and a liquid material flowing into thespaces around and between the seed elements within the matedhalf-shells.

The Embodiment of FIG. 3 is a System for Manufacturing Radiation TherapySeed Strands

FIG. 3 is a schematic of an embodiment of a system for manufacturinginterstitial radiation therapy seed strands of the invention.

The Embodiment of FIGS. 4A through 4C is a System for ManufacturingRadiation Therapy Seed Strands Using Extruded Strand Housings

FIG. 4A is an enlarged side view of an embodiment of the invention forextruding a seed housing in the shape of a tube.

FIG. 4B is an enlarged side view of the device in FIG. 4A with acomponent seed loader,

FIG. 4C is an enlarged side view of an embodiment the seed loader of theinvention for use with the seed housing of FIG. 4A.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

In accordance with an embodiment of the invention, a substantiallyaxially, semi-rigid and radially or laterally flexible elongated membermade of material, which is bio-absorbable in living tissue, is providedfor insertion in tumors. A plurality of radioactive seeds areencapsulated and positioned in a predetermined array in the member inthe desired spaced relationships.

The seeds can be of various types having low energy and low half-lifesuch as Iodine seeds, known as I-125 seeds, consisting of a weldedtitanium capsule containing iodine 125 absorbed on a silver rod, orPalladium 103 seeds. Examples of radioactive seeds used to manufacturethe therapeutic element appear in Table 1 below.

TABLE 1 Seed Manufacturers and Common Types of Seeds. PART NUMBERMANUFACTURER SEED NAME IODINE¹²⁵ 80040-A Amersham 6702 OncoSeed 80040-BAmersham 6711 RAPID Strand 80040-C North American Scientific IoGold80040-D Best Industries BEST Iodine-125 80040-E Bebig Symmetra 80040-FMills Biopharmaceuticals ProstaSeed 80040-G Syncor PharmaSeed 80040-HInternational Isotopes IsoStar 80040-I Implant Sciences I-Plant 80040-JInternational Brachytherapy InterSource-125 80040-K Source Tech STM125180040-L DRAXIMAGE, Inc. BrachySeed PALLADIUM¹⁰³ 80035-A North AmericanScientific Pd Gold 80035-B Theragenics Theraseed 200 80035-C BestIndustries BEST Palladium-103 80035-D International BrachytherapyInterSource 103

Additionally, seeds can be manufactured using iridium 192, cesium 131,gold 198, yttrium 90 and phosphorus 32. Further radioactive isotopesused to manufacture seeds are not limited to these examples, but caninclude other sources of different types of radiation. In addition it isto be understood that other types of seeds can be used. In particular,seeds such as those described in U.S. Pat. No. 6,248,057, which patentis incorporated herein by reference and which is entitled AbsorbableBrachytherapy and Chemotherapy Delivery Devices and Methods, can be usedwith the present invention. These seeds include radiation deliverydevices, drug delivery devices, and combinations of radiation and drugdelivery devices in the form of beads, seeds, particles, rods, gels, andthe like. These particular seeds are absorbable wherein the radiationelement or drug delivery element is contained within, for example,absorbable polymers such as those listed below or in theabove-referenced patent. In such seeds, the bio-absorbable structure canhave a predefined persistence which is substantially longer than a halflife of the radioactive element contained in the bio-absorbablestructure. These above bio-absorbable seeds can be used in the samemanner as the seeds described herein with respect to the invention.

The substantially axially, semi-rigid, and radially flexible elongatedmember may be made of any of the natural and/or synthetic bio-compatibleand bio-absorbable materials. Natural and synthetic polymers andcopolymers can be used. Examples of synthetic bio-absorbable polymermaterials are the polymers and copolymers of glycolide and lactide,polydioxanone and the like. Such polymeric materials are more fullydescribed in U.S. Pat. Nos. 3,565,869, 3,636,956, 4,052,988 and EuropeanPatent Application 30822 all of which are incorporated herein byreference. Specific examples of bio-absorbable polymeric materials thatcan be used to produce the substantially axially stiff and radiallyflexible elongated member of embodiment of the present invention arepolymers made by ETHICON, Inc., Somerville, N.J., under the trademarks“MONOCRYL” and “MAXON” which material is incorporated herein byreference.

Table 2below provides examples of polymers (and manufacturers) suitablefor use in producing embodiments the therapeutic member of theinvention. A further discussion of such biodegradable polymers can befound in an article by John C. Middleton and Arthur J. Tipton entitled“Synthetic Biodegradable Polymers as Medical Devices,” published March1998 in Medical Plastics and Bio-materials which article is incorporatedherein by reference.

TABLE 2 Biodegradable polymers, properties and degradation time.DEGRADA- MELTING GLASS- TION POLY- POINT TRANSITION MODULUS TIME MER (°C.) TEMP (° C.) (Gpa)^(a) (MONTHS)^(b) PGA 225–230 35–40 7.0  6 to 12LPLA 173–178 60–65 2.7 >24 DLPLA Amorphous 55–60 1.9 12 to 16 PCL 58–63(−65)–(−60) 0.4 >24 PDO N/A (−10)–0   1.5  6 to 12 PGA- N/A N/A 2.4  6to 12 TMC 85/15 Amorphous 50–55 2.0 5 to 6 DLPLG 75/25 Amorphous 50–552.0 4 to 5 DLPLG 65/35 Amorphous 45–50 2.0 3 to 4 DLPLG 50/50 Amorphous45–50 2.0 1 to 2 DLPLG ^(a)Tensile or flexural modulus. ^(b)Time tocomplete mass loss. Rate also depends on part geometry.

The final hardness of the polymer of elongate member should preferablybe in a range from 20 to 80 durometer and more preferably in the rangeof 20–40 durometer. The bio-absorbable material should preferably beabsorbed in living tissue in a period of time of from about 70 to about120 days, but can be manufactured to be absorbed anywhere in a rangefrom 1 week to 1 year, depending on the therapeutic plan for eachspecific patient. Preferably the bio-absorbable material is selected toabsorb about when the half-life of the radioactive seeds is reached.

The member or strand is fashioned with a manufacturing method known asinsert or compression molding. The radioactive seeds are placed into afixture that spaces the seeds at the appropriate intervals in a cavitythat is shaped to the desired final dimensions of the elongated member.All the spacings can be of different lengths, if the preoperativetherapeutic plan so specifies. The synthetic polymer is introduced intothe mold at a temperature that is above the melt point of the polymer.The polymer flows around the seeds within the cavity, surrounds theseeds and fills in the spaces between the seeds. After the mold hascooled, it is disassembled, and the finished elongated member isremoved. Because the polymer flows at temperatures significantly greaterthan 250° F., the therapeutic element can easily be steam sterilizedbefore implantation.

As specified above, the elongated member encapsulating radioactive seedsmay be fashioned using compression molding techniques. Compressionmolding forms the molded piece in a two part mold where the polymermaterial is placed within the cavities of the mold in a liquid state.The seeds are placed in position within the cavities filled with thepolymer and the mold is closed and compressed, then cooled to form apiece that conforms to the shape of the closed cavity.

The strand can also be fashioned from two half-shells made from the samematerial described above. The member or strand is fashioned by sealingthe seed elements between the two elongate half-shells and fusing thehalf-shells by heat or some other method. The seed elements can beplaced within two half-shells and liquid material or polymer can beflowed into the center of the unassembled or assembled half-shells,filling all space not occupied by seed elements or spacers.

The seed strand can also be fashioned by producing a catheter or hollowmember by extrusion. The material or polymer is placed into a chamberhaving a die and a mandrel. Pressure is applied by a piston in order topush the material through an opening between the die and the mandrel.During this process, the opening of the die forms the template for theouter wall of the catheter while the mandrel forms the interior bore.The radioactive seeds may then be inserted into the bore of the catheterduring the extrusion process or thereafter. The radioactive seeds may bespaced at variable intervals specific to the treatment goals of the enduser. All the spacings can be of different lengths, if the preoperativetherapeutic plan so specifies.

The manufacturing process also can make the member echogenic. In thecase of the molding of the elongated member, air can be entrapped in thepolymer material. During the cooling stage of the molding process, themold is placed in a vacuum chamber and the air in the chamber isevacuated. This causes the entrapped air in the mold to come out ofsolution from the polymer, and as the mold cools, this air is entrappedwithin the cooling polymer in the form of minute bubbles suspended inthe plastic.

Air is a strong reflector of ultrasound energy, since the inherentimpedance of air is many times greater than body tissue. When theelongated member is introduced into the body and imaged with ultrasound,the elongated member is clearly visible in the resulting image, and isthus echogenic.

The resulting elongated member is now a single solid monofilament of thepolymer with the seeds spaced within the monofilament and encapsulatedat the appropriate intervals. The member is generally very radiallyflexible such that it can be bent back upon itself in a circle withoutkinking. However, the member has sufficient column strength along itslongitudinal axis so that the member can be urged out of a hollow needlewithout the member folding upon itself. Again, the intervals can beselected to be any distance or combination of distances that are optimalfor the treatment plan of the patient.

Based on the above it is evident that the present invention provides foran embodiment having an elongated member which is comprised of abiodegradable polymer which encapsulates a plurality of spacedradioactive therapeutic seeds. The seeds can be spaced in custom mannerso that each member or strand is designed for the particular patient.That is to say that the spacing between each seed pair in a strand ormember can be different for each seed pair. Further each individualstrand can have an entirely different seed spacing pattern than the nextstrand or member. Characteristically or typically for a surgicalprocedure, up to twenty-five of such strands or members are used toencircle the organ or tumor that is affected.

Further such an arrangement provides for a strand or member that isstiff along its longitudinal axis. That is to say that the strand ormember has column strength or stiffness while the strand or member isflexible in the direction which is radial or substantially perpendicularto the longitudinal axis. Accordingly the strand or member in apreferred embodiment is able to bend back upon and touch itself, whenformed in a characteristic length.

In other embodiments, the strand or member can be made with theincorporation of drugs and/or hormones and/or other therapeutics whichare embedded in or formed in the polymer and/or seeds. Thus theembodiment of the invention can deliver not only radioactive seeds, butsuch therapeutic drugs, hormones and other therapeutic devices. Inaddition the strand or member can deliver heated seeds such as providedby ATI Medical. Then seeds can be preferably heated to from about six(6) degrees centigrade to about seventy (70) degrees centigrade prior tobeing inserted into a patient in a preferred embodiment. ATI Medical islocated at (www.ATImedical.com), and reference to such heated seeds isincorporated herein by reference.

It should be understood that other seed types can be used with thepresent invention. Thus for example in addition to the aboveencapsulated seeds, seeds which are made of radioactive or coiled wirescan be embedded in the polymer and be within the spirit and scope of theinvention. These seeds can be individual seeds which are spaced within apolymer or a continuous seed which extends the length of the strand ormember.

Further to the invention, as discussed above, it should be understoodthat the strand or member can be made echogenic by the incorporation of,for example, air bubbles 32 in the polymer spaces between the seeds, ascan be seen in FIGS. 1 and 3. These air bubbles or pockets can be formedin the polymer in ways identified above and other ways known to one ofskill in the art.

According to the above, the advantages of the improved delivery systemsubmitted of the present invention are:

1. The substantially axially stiff and radially flexible elongatedmember allows controlled placement of the plurality of radioactive seedsthat are encapsulated and positioned in a predetermined array in themember without migration of the individual radioactive seeds during thetime the seeds are treating the tumor.

2. The fixed linear positioning of the seeds minimizes “hot” and “cold”radiation spots due to undesirable movement of the seeds.

3. The normal tissue is spaced away from the seed surface by thethickness of the body of polymer, to decrease necrosis from a high localdose.

4. The axial stiffness of the elongated member allows the elongatedmember to be urged out of the needle as the needle is withdrawn, withoutthe member jamming in the needle, by collapsing or expanding as theneedle is withdrawn from the tumor site.

5. The radial flexibility of the elongated member allows locationalaccuracy to be maintained as the gland shrinks to pre-procedural size,as the swelling that occurs during tissue disruption and needlemanipulation recedes.

6. Increased speed of implant resulting in reduced surgical time andhealth care provider radiation exposure.

Method of Delivering Customized Strands and/or Members Per A TherapeuticPrescription

As is known in the industry, there is software which can be used toprovide branchytherapy treatment planning guides which are customizedfor each individual patent. Such software is provided by Rossmed whichis located at Ross Medical, 7100 Columbia Gateway Drive, Suite 160,Columbia, Md. 21046. This particular software, which is incorporatedherein by reference, is known as the Strata suite, which software helpsphysicians to develop and visualize low dose rate brachytherapytreatment plans for treating malignant tumors in human tissue. Thetreatments entail the use of radioactive seed sources which areimplanted adjacent to the malignant tissue. The Strata software usesimaging to create a three dimensional reconstruction of the patient'sanatomy. The software is able to plan the placement of the seeds withinthe target. The radiation dose that is delivered to the target can becomputerized and visualized using the software. The software can thenspecify an optimal number of strands or members along with optimal seeddosages and spaces between seeds. At times the loading plans sospecified cannot be optimized by the physician in preparing the seed andspacer loads for the needles, as the spacers come in only predefinedlengths.

Accordingly with the present invention, the software can be used toprepare a prescription which optimizes the number of members or strands,and placement and spacing of seeds for each of the strands or members.This optimization plan can then be sent to a manufacturing site. Byusing the techniques of an embodiment of the present invention, anoptimized strand or member can be created with the specified number ofseeds and the specified distances between each seed pair. Once thisprescription is filled at the manufacturing site, the custom strand ormember can be sent back to the physician for treatment of the patient.With such an arrangement, radiation patterns can be optimallyestablished for the treatment of each patient. Further the preparationtime for the physician is greatly diminished as the physician does nothave to hand assemble and hand load the seeds and spacers into theneedle.

Further even if the physician were to use a prescription provided by theabove software, with prior manufacturing techniques, the physician wouldonly receive from the manufacturing facility a strand or member whichhas seeds spaced at predefined intervals, which are the lengths or thepre-manufactured spacers. Accordingly optimal treatment as provided bythe custom strands or members manufactured according to the presentinvention could not be realized.

The Embodiments of FIGS. 1A through 1C Represent a Delivery System andMethod for Interstitial Radiation Therapy

In FIG. 1A, the therapeutic elongated element or member or matrix orstrand 104 is displayed having the semi-rigid, radially flexible polymer106 and the radioactive seeds 108. As can be seen in FIG. 1A, thepolymer fills the spacing segments 110 in a contiguous manner to fashionthe total elongate member.

FIG. 1C shows a side view of the brachytherapy device 112. The needle114 is shown partially broken away and has a sheath component 116, andis loaded with the therapeutic element or member 104. The beveled end118 of the needle 114 is plugged with a bio-compatible substance 120.The plug prevents fluids and tissue from entering the needle and comingin contact with the member 104 prior to the placement of the member orstrand 104 adjacent the tumor. The plug 120 can be made out of a bonewax or can be made of one of the bio-absorbable polymers or copolymerslisted herein. Further the plug can be the end of the member or strand104 that is heated and reflowed after the strand or member is insertedinto the needle. A stylet or stylus 122 is inserted into the needleuntil it meets the therapeutic element or member 104. Then the needle114 is inserted into the site and the therapeutic member 104 isgradually extruded from the needle via the static force of thestationary stylus 122, as the needle 114 is pulled back.

The Embodiments of FIGS. 2A through 2E Represent a InterstitialRadiation Therapy Seed Strands Constructed with Half-Shell StrandHousings

In FIG. 2A, the elongated members shaped like half-shells 201A, B areshown. The elongate members 201A, B may be composed of a bioabsorbablematerial such as previously described and such as previously listed inTable 2. The seed elements 208 and spacers 209 are placed within one ofthe half-shells 201A. Seed elements 208 can be coated with or containany low energy short half-life radioisotope, such as previously listedin Table 1, and/or a drug and/or hormone. The half-shells 201A, B canthen be mated, containing the seed elements 208 and spacers 209 as shownin FIG. 2A. To form the therapeutic element, the half-shells 201A, B arethen heated, fusing the half-shells 201A, B and fixing the seed elements208 and spacers 209 inside.

Alternatively, a bioabsorbable material can be flowed into thehalf-shell having appropriate spaced seeds and without spaces (FIG. 2C).The flowed in bioabsorbable materials maintains the appropriate spacing.As the bioabsorbable material is flowed in, the seeds are maintained inposition by manufacturing fingers or by being urged into the material ofthe half-shell. After the material is flowed in, the two half-shells areassembled and if required, heated to form the final assembly. Also it isunderstood that a polymer can be flowed into a half shell prior to theassembly of the two half shells, together. Thereafter, the two halfshells can be assembled and heated, if required, for fusing the assemblytogether.

FIG. 2D shows a side view of elongate solid member half-shells 201 withindentations 210 for seed elements 208. The indentations can have avariety of shapes from those that follow the contour of the seeds toother shapes such as, for example, the rectangular shapes. Thehalf-shells 201 are composed of material as described with respect toFIGS. 1A to 1C. The seed elements are also described with respect toFIGS. 1A to 1C. The seed elements 208 are placed into the indentations210 and the two half-shells 201 mated. The half-shells 201 are thenfused by heating or other means, fixing the seed elements 208 inside andforming the therapeutic element.

FIG. 2E shows a side view of a method of making a therapeutic element.Two half-shells 201 have been mated with seed elements 208 inside. Thehalf-shells 201 and seed elements 208 are described above in FIGS.2A–2D. The half-shells 201 have indentations 232 for the seed elements208 and remaining dead space 228 between the seed elements 208. The seedelements 208 can be held tightly in the indentations 232 of theassembled half-shells 201, and as such, the seed elements 208 have holes226 through their centers to allow material 234 to flow through theentire strand. Material 234 is injected into the mated half-shells 201via a device 236 and the material 234 fills all the remaining space inthe indentations 232 and dead space 228 between the seed elements 208.The therapeutic element is formed when the material 234 solidifies,fusing the half-shells 201 and fixing the seed elements 208 in placewithin the therapeutic element. Upon solidifying, the material 234 isaxially rigid and radially flexible and may be bioabsorbable or composedof any of the polymers listed in Table 2. Alternatively, solid seeds canbe used with some space being present between the seeds and indentationin the assembled preformed half shell. The indentations keep the seedsin place and allow the polymer to flow past the seeds. Alternatively,the indentations can have fingers that keep the seeds from touching thewalls of the indentations of the half shells. The polymer can thus flowinto the bore of the assembled half shells and past the fingers.

The Embodiment of FIG. 3 is a System for Manufacturing Radiation TherapySeed Strands

In FIG. 3, a schematic of one embodiment of the present invention isshown. The pictured components of the system 322 are not necessarilyproportional to each other. The embodiment uses first and secondelongate half-shell members 301A, 301B. The elongate half-shell members301A, 301B may be composed of any material that is axially rigid andradially flexible when assembled with seeds into a strand. Such amaterial may be a bioabsorbable polymer selected from those listed aboveand also in Table 2. Within the second half-shell elongate member 301Bis positioned seed elements 308. The seed elements can be spread withthe same or different intervals as required for treating the patient.The seed elements 308 may be coated with or contain a low energy, shorthalf-life radioisotope such as those listed above and also in Table 1.The seed elements 308 may also be coated with or contain a drug orhormone. Alternatively, the seed elements 308 can, at least in part, beconstructed of a bioabsorbable material. A heating element 324 is alsodepicted. A computer 330 is connected to a robotic arm controller 328,which operates a robotic arm 326.

To manufacture a seed strand, the computer 330 processes a seed loadingprotocol based on a treatment plan specific to the patient as describedabove. The computer 330 then communicates with the controller 328 whichcontrols the robotic arm 326. Based upon this information, the roboticarm 326 picks the seed elements 308 according to the treatment plan andseed loading protocol and places the seed elements 308 in one half-shellelongate member 301B. Then the robotic arm 326 or another robotic arm(not shown) picks up the other elongate half-shell member 301A and matesit to the elongate member 301B containing the seeds. Next, the roboticarm 326 places the half-shell assembly 301A,B containing the seedelements 308 into a heating element 324 where the half-shells 301A,B areheated and fused, fixing the seed elements 308 in place. Alternatively,liquid material can be injected in 301A,B, whether the half shells areassembled or unassembled, and around the seed elements 308 usingtechniques described above. When the material solidifies, it fuses thehalf-shells 301A,B, fixing the seed elements 308 in place, and theassembly is axially rigid and radially flexible.

The system 322 can also provide a facility to test each of the seeds.The system 322 can be compact and if desired be configured as atable-top unit which can be located at a hospital or other treatmentsite and manufacture seed strands as they are needed for a patient.Based on the above it is evident that the present invention provides fora system and method for manufacturing interstitial radiation therapystrands that produce an elongated member which is comprised of abiodegradable polymer which encapsulates a plurality of spacedradioactive therapeutic seeds. The seeds can be spaced in a custommanner so that each member or strand is designed for the particularpatient. That is to say that the spacing between each seed pair in astrand or member can be different for each seed pair. Further eachindividual strand can have an entirely different seed spacing patternthan the next strand or member.

The Embodiment of FIGS. 4A through 4C is a System for ManufacturingRadiation Therapy Seed Strands Using Extruded Strand Housing

FIG. 4A depicts a system 446 for forming a seed housing in the shape ofa tube and of, in this particular embodiment, a bioabsorbable polymer asdescribed above. The system 446 includes a mandrel 438, a piston 444 anda die 424. As the piston extrudes the material 440 over the mandrel 438and through the die 424, an elongate hollow member or seed housing isformed that is shaped like a catheter. The resulting interstitialradiation therapy device is much longer than its width. The width ofsuch a device should be narrow enough to be accommodated into a needlefor implantation into the treatment site as described above. In itsfinal state assembled with seeds, the material 440 must be axially rigidand radially flexible and can be any of the polymers listed in Table 2above. The material 440 may also be bioabsorbable.

FIG. 4B shows the extrusion apparatus from FIG. 4A with seed elements408 and modified to have a seed pusher 442, wherein the seed elementsare inserted (loaded) simultaneously with extrusion. The material 440 isextruded through the opening of the die 424 by pressure from the polymerpusher 438 forming a catheter or seed housing with a bore. A seed pusher442 then inserts seed elements 34 into the bore of the catheter at thedesired location. The seed elements 408 may be coated or contain any lowenergy, short half life radioisotope such as those listed in Table 1above. The seed elements 408 may also be coated with or contain a drugor hormone. The seed elements 408 may be composed of a radio-opaquemetal such as titanium or a bioabsorbable polymer.

FIG. 4C shows a seed pusher 450 as it inserts a seed element 408 to thedesired location into the bore of the seed housing that had beenpreviously extruded in accordance with FIG. 4A. For all the methods anddevices discussed above and depicted, the spacing between seeds orcapsules containing seeds can be optimized and custom set between seedor capsule pairs per a prescription treatment plan.

The foregoing description of the preferred embodiments of the presentinvention has been provided for the purposes of illustration anddescription. It is not intended to be exhaustive or to limit theinvention to the precise forms disclosed. Many modifications andvariations will be apparent to the practitioner skilled in the art.Embodiments were chosen and described in order to best describe theprinciples of the invention and its practical application, therebyenabling others skilled in the art to understand the invention, thevarious embodiments and with various modifications that are suited tothe particular use contemplated. It is intended that the scope of theinvention be defined by the following claims and their equivalents.

1. A method for embedding radioactive seed elements in a materialcomprising: extruding a member with a bore from the material; andloading said bore of said member with the radioactive seed elements tospace the radioactive seed elements at variable positions; wherein theloading step occurs simultaneously with the extruding step.
 2. Themethod of claim 1 wherein said loading step includes introducingvariable spacing between each of the radioactive seed elements.
 3. Themethod of claim 1 wherein said material is biocompatible andbioabsorbable.
 4. The method of claim 1 wherein said material containsone of a drug and a hormone.
 5. The method of claim 1 wherein saidmaterial is made to be echogenic.
 6. The method as in claim 1 whereinthe loading step is carried out according to a pre-operative therapeuticplan of a patient.
 7. The method as in claim 1 further comprising usingthe material in the extruding step wherein the material is selected fromthe group consisting of PGA, LPLA, DLPLA, PCL, PDO, PGA-TMC, 85/15DLPLG, 75/25 DLPLG, 65/35 DLPLG, and 50/50 DLPLG.
 8. The method as inclaim 1 further comprising using the material in the extruding stepwherein the material is selected from the group consisting of polymersof glycolide, polymers of polydioxanone, copolymers of glycolide, andcopolymers of polydioxanone.
 9. The method as in claim 1 furthercomprising using the material in the extruding step wherein the materialis selected from the group consisting of naturalbiocompatible/bioabsorbable polymers and syntheticbiocompatible/bioabsorbable polymers.
 10. The method as in claim 1further comprising the step of incorporating therapeutic agents into thematerial.
 11. The method as in claim 1 further comprising the step ofincorporating therapeutic agents into the radioactive seed elements. 12.The method as in claim 1 further comprising: providing a systemcomprising: a mandrel; a piston; and a die; wherein the extruding stepfurther comprises applying pressure to the material with the piston toextrude the material over the mandrel and through the die, forming themember with a bore therethrough.
 13. The method as in claim 1 furthercomprising using the seed pusher in the loading step to load theradioactive seed elements according to a pre-operative plan of apatient.
 14. A method for making an interstitial radiation therapy seedstrand comprising: extruding an elongate member with a bore from amaterial that is axially rigid and radially flexible when loaded withradioactive seed elements; and inserting said radioactive seed elementsinto said bore at variable positions using a seed pusher; wherein theinserting step occurs simultaneously with the extruding step.
 15. Themethod of claim 14 wherein said inserting step includes placing theradioactive seeds at varying intervals within the bore.
 16. The methodof claim 14 wherein said elongate member with a bore is heated to fixsaid radioactive seed elements within the bore.
 17. The method of claim14 wherein said material is biocompatible and bioabsorbable.
 18. Themethod of claim 14 wherein said material contains one of a drug and ahormone.
 19. The method of claim 14 wherein said material is made to beechogenic.
 20. A method for embedding radioactive seed elements in amaterial comprising: extruding a member with a bore from the material;and loading said bore of said member with the radioactive seed elementsusing a seed pusher to space the radioactive seed elements at variablepositions; wherein the loading step occurs simultaneously with theextruding step.
 21. A method for embedding radioactive seed elements ina material comprising: providing a system comprising: a mandrel; apiston; and a die; extruding a member with a bore from the material; andloading the bore of the member with the radioactive seed elements usinga seed pusher to space the radioactive seed elements at variablepositions; wherein the extruding step further comprises applyingpressure to the material with the piston to extrude the material overthe mandrel and through the die, forming the member with a boretherethrough; and wherein the extruding and loading steps are performedsimultaneously.
 22. An extrusion method for embedding radioactive seedelements in a material comprising: providing a system comprising: a seedpusher; a mandrel; a piston; and a die; extruding the material over themandrel and through the die with the piston, wherein the piston is usedto apply pressure to the material, to create an elongate axially stiffand radially flexible hollow member comprising a bore; and loading theradioactive seed elements into the bore according to a pre-operativeplan customized to a patient, the loading step including use of the seedpusher; wherein the extruding step and the loading step aresimultaneously performed using the system provided in the providingstep.
 23. The method as in claim 22 further comprising providing theradioactive seed elements wherein said radioactive seed elements furthercomprise a radio-opaque metal.
 24. The method as in claim 22 furthercomprising providing the radioactive seed elements wherein saidradioactive seed elements further comprise a bioabsorbable polymer. 25.An extrusion method for embedding radioactive seed elements in amaterial comprising: providing a system comprising: a mandrel; a piston;and a die; extruding the material over the mandrel and through the diewith the piston, wherein the piston is used to apply pressure to thematerial, to create an elongate hollow member comprising a bore; andloading the radioactive seed elements into the bore according to apre-operative plan customized to a patient; wherein the loading stepoccurs simultaneously with the extruding step.
 26. The method as inclaim 25 wherein the loading step further comprises inserting theradioactive seed elements with a seed pusher.
 27. The method as in claim25 further comprising providing the radioactive seed elements whereinsaid radioactive seed elements further comprise a radio-opaque metal.28. The method as in claim 25 further comprising providing theradioactive seed elements wherein said radioactive seed elements furthercomprise a bioabsorbable polymer.